A Study of Nemtabrutinib Plus Venetoclax vs Venetoclax + Rituximab (VR) in Second-line (2L) + Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) (MK-1026-010/BELLWAVE-010)

Eligibility Criteria

• * Confirmed diagnosis of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and active disease clearly documented to initiate therapy.
• * Deletion (Del) (17p) status, tumor protein 53 (TP53) mutation status, immunoglobulin heavy chain gene (IGHV) mutation status and Bruton's tyrosine kinase (BTK)-C481 mutation status results required before randomization for Part 2 participants only.
• * Relapsed or refractory to at least 1 prior available therapy.
• * Have at least 1 marker of disease burden.
• * Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 within 7 days before randomization.
• * Has a life expectancy of at least 3 months.
• * Has the ability to swallow and retain oral medication.
• * Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV deoxyribonucleic acid (DNA) viral load before randomization.
• * Participants with history of hepatitis C virus (HCV) infection are eligible if HCV ribonucleic acid (RNA) viral load is undetectable at screening.
• * Participants with human immunodeficiency virus (HIV) who meet ALL eligibility criteria.
• * Participants with adequate organ function with specimens collected within 7 days before the start of study intervention.
• * If capable of producing sperm, participant agrees to eliminate Nemtabrutinib: 12 days, Venetoclax: 1 month (30 days), Rituximab (rituximab biosimilar): not applicable; abstains from penile-vaginal intercourse as their preferred and usual lifestyle; OR uses prescribed contraception.
• * Participant assigned female sex at birth are eligible to participate if not pregnant or breastfeeding and are not a person of childbearing potential (POCBP) OR is a POCBP and uses a contraceptive method that is highly effective, has a negative highly sensitive pregnancy test, and abstains from breastfeeding.
• * Has an active hepatitis B virus/ hepatitis C virus (HBV/HCV) infection.
• * Has gastrointestinal (GI) dysfunction that may affect drug absorption.
• * Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
• * Has diagnosis of Richter Transformation or active central nervous system (CNS) involvement by CLL/SLL.
• * Has an active infection requiring systemic therapy, such as intravenous (IV) antibiotics, during screening.
• * HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease and/or acquired immune deficiency syndrome (AIDS)-defining opportunistic infection in the past 12 months before screening.
• * Has QT interval corrected (QTc) prolongation or other significant electrocardiogram (ECG) abnormalities.
• * Has a known allergy/sensitivity to nemtabrutinib or contraindication to venetoclax/rituximab (or rituximab biosimilar), or any of the excipients.
• * Has history of severe bleeding disorders (eg, hemophilia).
• * Has received prior systemic anticancer therapy within 5 half-lives or 4 weeks (if prior therapy was a monoclonal antibody) before randomization.
• * Has received prior B-cell lymphoma 2 inhibitor(s) (BCL2i) including venetoclax or Non-covalent Bruton's tyrosine kinase inhibitor (BTKi).
• * Is currently being treated with p-glycoprotein (P-gp) substrates with a narrow therapeutic index, cytochrome P450 3A (CYP3A) strong or moderate inducers or CYP3A strong inhibitors.
• * Has received a live or live attenuated vaccine within 30 days before the first dose of study intervention.
• * Has received an investigational agent or has used an investigational device within 4 weeks before study intervention administration.
• * Has a known psychiatric or substance use disorder that would interfere with the participant's ability to cooperate with the requirements of the study.
• * Participants who have not adequately recovered from major surgery or have ongoing surgical complications.